Elucidation of molecular mechanism that controls the maintenance of retinal stem cells

视网膜的边缘区域含有视网膜干细胞，其持续增殖并长时间保持未分化。我们以前已经确定了一个信号分子Wnt 2b作为视网膜干细胞因子，维持视网膜干细胞的未分化状态。在本研究项目中，我们研究了Wnt信号的下游通路，特别关注转录因子。我们已经发现，Wnt激活多个转录因子，包括c-myc，这反过来又协同激活转录抑制因子c-hairy 1。我们还发现，c-hairy 1的激活反过来是必要的，足以抑制视网膜干细胞的分化。因此，c-hairy 1作为Wnt信号传导的下游节点发挥功能，以维持视网膜干细胞。

The marginal region of the retina contains retinal stem cells that continue to proliferate and remain undifferentiated for a long period. We have previously identified a signaling molecule Wnt2b as a retinal stem cell factor that maintains undifferentiated state of the retinal stem cells. In this research project, we investigated downstream pathway of the Wnt signaling, especially focusing on transcription factors. We have found that Wnt activates multiple transcription factors including c-myc, which in turn cooperatively activate a transcriptional repressor c-hairy1. We have also revealed that the activation of c-hairy1 in turn was necessary and sufficient to inhibit differentiation of the retinal stem cells. Thus, c-hairy1 functions as a node downstream of Wnt signaling to maintain the retinal stem cells.